The role of carbohydrates in most glycoproteins is not known. Moreover, there is little known about the endocrine and developmental regulation of carbohydrate structure. Using newly developed methods of high performance liquid chromatography, we have shown that thyrotropin (TSH) from hypothyroid rodents has more sialylated and less sulfated chains. Similarly, in development there is an increase in sialylation as well as more complex carbohydrate chains. Such changes correlate with a delay in metabolic clearance rate and presumably increased in vivo bioactivity. Inhibitors of carbohydrate processing to final complex sugar structures affect the secretion and sorting of TSH. These studies suggest that carbohydrate processing of glycoproteins may be regulated and affect multiple biological functions.